Medicine and Health Sciences Commons^™

Endoscopic Retrograde Cholangiopancreatography-Related Early Perforations: A Study Of Effects Of Procedure Duration, Complexity, And Endoscopist Experience, Mark Aloysius, Hemant Goyal, Tejas Nikumbh, Niraj James Shah, Ghassan M Hammoud, Pritesh Mutha, Mairin Joseph-Talreja, Savio John, Ganesh Aswath, Vaibhav Wadhwa, Nirav Thosani

Faculty, Staff and Student Publications

BACKGROUND: Perforations (Perf) during endoscopic retrograde cholangiopancreatography (ERCP) are rare (< 1%) but potentially fatal events (up to 20% mortality). Given its rarity, most data is through case series studies from centers or analysis of large databases. Although a meta-analysis has shown fewer adverse events as a composite (bleeding, pancreatitis, Perf) during ERCP performed at high-volume centers, there is very little real-world data on endoscopist and center procedural volumes, ERCP duration and complexity on the occurrence of Perf.

AIM: To study the profile of Perf related to ERCP by center and endoscopist procedure volume, ERCP time, and complexity from a national endoscopic repository.

METHODS: Patients from clinical outcomes research initiative-national endoscopic database (2000-2012) who underwent ERCP were stratified based on the endoscopist and center volume (quartiles), and total procedure duration and complexity grade of the ERCP based on procedure details. The effects of these variables on the Perf that occurred were studied. Continuous variables were compared between Perf and no perforations (NoPerf) using the Mann-Whitney U test …

Internet Analytics Of An Innovative Digital Educational Resource Of Type 1 Diabetes Hellotype1 In Local Languages For People Living With Diabetes Families And Healthcare Professionals In Southeast Asia, Sze May Ng, I V Malene, Thy Khue Nguyen, Khuong Le, Yang Xian Lucas Lim, Ngee Lek, Samantha Seal, Steffen Yun Tange, Azriyanti Anuar Zaini, Taninee Sahakitrungruang, Anne Charlotte Ficheroulle

Faculty, Staff and Student Publications

BACKGROUND: There is minimal data of health outcomes for Type 1 Diabetes (T1D) in Southeast Asia (SEA) where government funding of insulin and blood glucose monitoring either do not exist or is limited. The full impact of Covid-19 pandemic on the national economies of SEA remain unknown. In the midst of the pandemic, in 2021, HelloType1 was developed by Action4Diabetes (A4D), a non-government organisation charity in collaboration with Southeast Asia local healthcare professionals as an innovative digital educational resource platform of T1D in local languages. HelloType1 was launched in Cambodia, Vietnam, Thailand and Malaysia in 2021 to 2022 with Memorandums …

Morphological Comparison Of Residual Ridge In Impression For Removable Partial Denture Between Digital And Conventional Techniques: A Preliminary In-Vivo Study, Yurika Ishioka, Junichiro Wada, Eung-Yeol Kim, Kazuki Sakamoto, Yuki Arai, Natsuko Murakami, Toshiki Yamazaki, Kensuke Takakusaki, Hironari Hayama, Miona Utsumi, Shusuke Inukai, Noriyuki Wakabayashi

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Although digital impression using an intraoral scanner (IOS) has been applied for removable partial denture (RPD) fabrication, it is still unclear how the morphology of a residual ridge recorded by digital impression would differ from that recorded by conventional impression. This in vivo study investigated the morphological difference in the recorded residual ridge between digital and conventional impressions. Vertical and horizontal displacements (VD and HD) in residual ridges recorded by digital and conventional impressions were assessed in 22 participants (15 female; mean age 78.2 years) based on the morphology of the tissue surface of in-use RPD. Additionally, the mucosal thickness …

Galectin-3 Cooperates With Cd47 To Suppress Phagocytosis And T-Cell Immunity In Gastric Cancer Peritoneal Metastases, Yibo Fan, Shumei Song, Yuan Li, Shilpa S Dhar, Jiankang Jin, Katsuhiro Yoshimura, Xiaodan Yao, Ruiping Wang, Ailing W Scott, Melissa Pool Pizzi, Jingjing Wu, Lang Ma, George A Calin, Samir Hanash, Linghua Wang, Michael Curran, Jaffer A Ajani

Faculty, Staff and Student Publications

UNLABELLED: The peritoneal cavity is a common site of gastric adenocarcinoma (GAC) metastasis. Peritoneal carcinomatosis (PC) is resistant to current therapies and confers poor prognosis, highlighting the need to identify new therapeutic targets. CD47 conveys a "don't eat me" signal to myeloid cells upon binding its receptor signal regulatory protein alpha (SIRPα), which helps tumor cells circumvent macrophage phagocytosis and evade innate immune responses. Previous studies demonstrated that the blockade of CD47 alone results in limited clinical benefits, suggesting that other target(s) might need to be inhibited simultaneously with CD47 to elicit a strong antitumor response. Here, we found that …

Baseline Extracellular Vesicle Mirna-30c And Autophagic Ctcs Predict Chemoradiotherapy Resistance And Outcomes In Patients With Lung Cancer, Diego De Miguel-Perez, Francisco Gabriel Ortega, Rosario Guerrero Tejada, Antonio Martínez-Única, Christine B Peterson, Alessandro Russo, Muthukumar Gunasekaran, Andres F Cardona, Victor Amezcua, Jose Antonio Lorente, Jose Expósito Hernández, Christian Rolfo, Maria Jose Serrano

Faculty, Staff and Student Publications

Concurrent chemoradiotherapy (cCRT) is the mainstay of treatment for patients diagnosed with locally advanced non-small cell lung cancer (NSCLC). One significant challenge in the effectiveness of this therapy is the potential development of resistance mechanisms, where autophagy up-regulation has been proposed as a key contributing factor. However, there is a lack of reliable biomarkers to predict outcomes on these patients. Interestingly, for addressing this gap, extracellular vesicles (EVs) and circulating tumor cells (CTCs) have emerged as potential sources of such biomarkers. In this study, we investigated EV-associated miRNAs and presence of autophagic CTCs in prospectively collected serial samples from 38 …

Dissociable Effects Of Alzheimer's Disease-Related Cognitive Dysfunction And Aging On Functional Brain Network Segregation, Ziwei Zhang, Micaela Y Chan, Liang Han, Claudia A Carreno, Ezra Winter-Nelson, Gagan S Wig

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Alzheimer's disease (AD) is associated with changes in large-scale functional brain network organization. Individuals with AD exhibit less segregated resting-state brain networks compared with individuals without dementia. However, declines in brain network segregation are also evident as adult individuals grow older. Determining whether these observations reflect unique or overlapping alterations on the functional connectome of the brain is essential for understanding the impact of AD on network organization and incorporating measures of functional brain network organization toward AD characterization. Relationships between AD dementia severity and participant's age on resting-state brain system segregation were examined in 326 cognitively healthy and 275 …

Indices Of Narrative Language Associated With Disability, Norah M Almubark, Gabriela Silva-Maceda, Matthew E Foster, Trina D Spencer

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Narratives skills are associated with long-term academic and social benefits. While students with disabilities often struggle to produce complete and complex narratives, it remains unclear which aspects of narrative language are most indicative of disability. In this study, we examined the association between a variety of narrative contents and form indices and disability. Methodology involved drawing 50 K-3 students with Individual Education Programs (IEP) and reported language concerns from a large diverse sample (n = 1074). Fifty typically developing (TD) students were matched to the former group using propensity score matching based on their age, gender, grade, mother’s education, …

Circulating Tumor Dna Monitoring On Chemo-Immunotherapy For Risk Stratification In Advanced Non-Small Cell Lung Cancer, Bruna Pellini, Russell W Madison, Merrida A Childress, Shoshana T Miller, Ole Gjoerup, Jason Cheng, Richard S P Huang, Michael Krainock, Pratyush Gupta, Wei Zou, David S Shames, Solomon Moshkevich, Marcus Ballinger, Minetta C Liu, Amanda Young, Minu K Srivastava, Geoffrey R Oxnard, Mark A Socinski

Faculty, Staff and Student Publications

PURPOSE: Chemoimmunotherapy (chemoIO) is a prevalent first-line treatment for advanced driver-negative non-small cell lung cancer (NSCLC), with maintenance therapy given after induction. However, there is significant clinical variability in the duration, dosing, and timing of maintenance therapy after induction chemoIO. We used circulating tumor DNA (ctDNA) monitoring to inform outcomes in patients with advanced NSCLC receiving chemoIO.

EXPERIMENTAL DESIGN: This retrospective study included 221 patients from a phase III trial of atezolizumab+carboplatin+nab-paclitaxel versus carboplatin+nab-paclitaxel in squamous NSCLC (IMpower131). ctDNA monitoring used the FoundationOne Tracker involving comprehensive genomic profiling of pretreatment tumor tissue, variant selection using an algorithm to exclude nontumor …

Novel Clinical Trial Designs With Dose Optimization To Improve Long-Term Outcomes, Peter F Thall, Yong Zang, Andrew G Chapple, Ying Yuan, Ruitao Lin, David Marin, Pavlos Msaouel

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Conventional designs for choosing a dose for a new therapy may select doses that are unsafe or ineffective and fail to optimize progression-free survival time, overall survival time, or response/remission duration. We explain and illustrate limitations of conventional dose-finding designs and make four recommendations to address these problems. When feasible, a dose-finding design should account for long-term outcomes, include screening rules that drop unsafe or ineffective doses, enroll an adequate sample size, and randomize patients among doses. As illustrations, we review three designs that include one or more of these features. The first illustration is a trial that randomized patients …

Phase 1 Study Of Vibecotamab Identifies An Optimized Dose For Treatment Of Relapsed/Refractory Acute Myeloid Leukemia, Farhad Ravandi, Asad Bashey, James Foran, Wendy Stock, Raya Mawad, Nicholas Short, Musa Yilmaz, Hagop Kantarjian, Olatoyosi Odenike, Anand Patel, Raman Garcha, William Barrett Ainsworth, Raphael Clynes, Jitendra Kanodia, Ying Ding, Huajiang Li, Steve Kye, Alice Mims

Faculty, Staff and Student Publications

Acute myeloid leukemia (AML), an aggressive malignancy with unmet medical need, lacks immunotherapeutic options. CD123, the cellular receptor for interleukin-3, expressed in AML is an attractive target for tumor-specific therapy. Vibecotamab (XmAb14045), a humanized bispecific antibody, monovalently binds both CD3 and CD123 to recruit cytotoxic T cells to kill CD123+ tumor cells. This phase 1 study's primary objectives were safety and tolerability and identification of a maximum tolerated dose/recommended dose for use as monotherapy in patients with relapsed/refractory AML. Identification of a recommended phase 2 vibecotamab dose comprised 3 step-up doses (Week 1), which were noted to reduce cytokine response …

Dhodh: A Promising Target In The Treatment Of T-Cell Acute Lymphoblastic Leukemia, Amy N Sexauer, Gabriela Alexe, Karin Gustafsson, Elizabeth Zanetakos, Jelena Milosevic, Mary Ayres, Varsha Gandhi, Yana Pikman, Kimberly Stegmaier, David B Sykes

Faculty, Staff and Student Publications

Patients with relapsed or refractory T-cell acute lymphoblastic leukemia (T-ALL) have a poor prognosis with few therapeutic options. With the goal of identifying novel therapeutic targets, we used data from the Dependency Map project to identify dihydroorotate dehydrogenase (DHODH) as one of the top metabolic dependencies in T-ALL. DHODH catalyzes the fourth step of de novo pyrimidine nucleotide synthesis. Small molecule inhibition of DHODH rapidly leads to the depletion of intracellular pyrimidine pools and forces cells to rely on extracellular salvage. In the absence of sufficient salvage, this intracellular nucleotide starvation results in the inhibition of DNA and RNA synthesis, …

The Landscape Of Alterations From 1407 Ultra-Rare Sarcomas From The Aacr Genie Database: Clinical Implications, Ryan A Denu, Justin T Moyers, Mohamed A Gouda, Anthony P Conley, Alexander J Lazar, Vivek Subbiah

Faculty, Staff and Student Publications

Purpose: Ultra-rare sarcomas (URS) comprise a group of orphan diseases with an incidence of ≤1/1,000,000 people per year. We aimed to assess clinically actionable genomic alterations in URS.

Experimental design: Data were extracted from the GENIE database using cBioPortal. OncoKB was used to assess for clinical actionability of mutations. Tumor mutational burden (TMB) was inferred from clinical sequencing data.

Results: Soft tissue (ST) URS made up 23.5% of ST sarcoma cases, and bone URS made up 16.5% of bone sarcoma cases. The most commonly mutated gene in all four groups was TP53. The most common fusions involved EWSR1. The most …

A Phase 1 Study Of Prophylactic Anakinra To Mitigate Icans In Patients With Large B-Cell Lymphoma, Paolo Strati, Andrew Jallouk, Qing Deng, Xubin Li, Lei Feng, Ryan Sun, Sherry Adkins, Swapna Johncy, Taylor Cain, Raphael E Steiner, Sairah Ahmed, Dai Chihara, Luis E Fayad, Swaminathan P Iyer, Sandra Horowitz, Loretta J Nastoupil, Ranjit Nair, Ahmed Hassan, Taher E Daoud, Misha Hawkins, Maria A Rodriguez, Elizabeth J Shpall, Jeremy L Ramdial, Partow Kebriaei, David S Hong, Jason R Westin, Sattva S Neelapu, Michael R Green

Faculty, Staff and Student Publications

No abstract provided.

Gasdermin D Permeabilization Of Mitochondrial Inner And Outer Membranes Accelerates And Enhances Pyroptosis, Rui Miao, Cong Jiang, Winston Y Chang, Haiwei Zhang, Jinsu An, Felicia Ho, Pengcheng Chen, Han Zhang, Caroline Junqueira, Dulguun Amgalan, Felix G Liang, Junbing Zhang, Charles L Evavold, Iva Hafner-Bratkovič, Zhibin Zhang, Pietro Fontana, Shiyu Xia, Markus Waldeck-Weiermair, Youdong Pan, Thomas Michel, Liron Bar-Peled, Hao Wu, Jonathan C Kagan, Richard N Kitsis, Peng Zhang, Xing Liu, Judy Lieberman

Faculty, Staff and Student Publications

Gasdermin D (GSDMD)-activated inflammatory cell death (pyroptosis) causes mitochondrial damage, but its underlying mechanism and functional consequences are largely unknown. Here, we show that the N-terminal pore-forming GSDMD fragment (GSDMD-NT) rapidly damaged both inner and outer mitochondrial membranes (OMMs) leading to reduced mitochondrial numbers, mitophagy, ROS, loss of transmembrane potential, attenuated oxidative phosphorylation (OXPHOS), and release of mitochondrial proteins and DNA from the matrix and intermembrane space. Mitochondrial damage occurred as soon as GSDMD was cleaved prior to plasma membrane damage. Mitochondrial damage was independent of the B-cell lymphoma 2 family and depended on GSDMD-NT binding to cardiolipin. Canonical and …

Cigarette Smoke Exposure Accelerates Aml Progression In Flt3-Itd Models, Mary Figueroa, Huaxian Ma, Mansour Alfayez, Daniel Enrique Morales-Mantilla, Fei Wang, Yue Lu, Marcos R Estecio, Katherine Y King, Eugenie Kleinerman, Seyed Javad Moghaddam, Naval Daver, Michael Andreeff, Marina Konopleva, Courtney Dinardo, Joya Chandra

Faculty, Staff and Student Publications

No abstract provided.

Pharyngeal Oxygen Delivery Device Sustains Manikin Lung Oxygenation Longer Than High-Flow Nasal Cannula, Jeramie B Hanson, John R Williams, Emily H Garmon, Phillip M Morris, Russell K Mcallister, Courtney N Shaver, William C Culp

Faculty, Staff and Student Publications

PURPOSE: Hypoxemia during a failed airway scenario is life threatening. A dual-lumen pharyngeal oxygen delivery device (PODD) was developed to fit inside a traditional oropharyngeal airway for undisrupted supraglottic oxygenation and gas analysis during laryngoscopy and intubation. We hypothesized that the PODD would provide oxygen as effectively as high-flow nasal cannula (HFNC) while using lower oxygen flow rates.

METHODS: We compared oxygen delivery of the PODD to HFNC in a preoxygenated, apneic manikin lung that approximated an adult functional residual capacity. Four arms were studied: HFNC at 20 and 60 liters per minute (LPM) oxygen, PODD at 10 LPM oxygen, …

Beyond Bacteria: How The Intratumor Mycobiome Modulates Lung Adenocarcinoma Progression, Zahraa Rahal, Humam Kadara

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Increasing evidence suggests that tumors harbor diverse microbiomes, adding complexity to the tumor microenvironment. In this issue of Cancer Cell, Liu et al. highlight the role of the intratumor mycobiome, specifically Aspergillus sydowii, in promoting lung adenocarcinoma progression. A. sydowii enhances the recruitment and activation of myeloid-derived suppressor cells via IL-1β signaling driven by the β-glucan-mediated Dectin-1/CARD9 pathway.

A Single-Cell Atlas Of Cd19 Chimeric Antigen Receptor T Cells, Xubin Li, Jared Henderson, Max J Gordon, Irtiza Sheikh, Loretta J Nastoupil, Jason Westin, Christopher Flowers, Sairah Ahmed, Linghua Wang, Sattva S Neelapu, Paolo Strati, Qing Deng, Michael R Green

Faculty, Staff and Student Publications

Li et al. present a resource of single-cell RNA sequencing (scRNA-seq) data from the infusion products of relapsed or refractory large B cell lymphoma (rrLBCL) patients treated with standard-of-care axicabtagene ciloleucel and identify features that are significantly different between products from responders and non-responders at 3-month followup by PET/CT, an important landmark for long-term outcomes.

Tumor-Resident Lactobacillus Iners Confer Chemoradiation Resistance Through Lactate-Induced Metabolic Rewiring, Lauren E Colbert, Molly B El Alam, Rui Wang, Tatiana Karpinets, David Lo, Erica J Lynn, Timothy A Harris, Jacob H Elnaggar, Kyoko Yoshida-Court, Katarina Tomasic, Julianna K Bronk, Julie Sammouri, Ananta V Yanamandra, Adilene V Olvera, Lily G Carlin, Travis Sims, Andrea Y Delgado Medrano, Tatiana Cisneros Napravnik, Madison O'Hara, Daniel Lin, Chike O Abana, Hannah X Li, Patricia J Eifel, Anuja Jhingran, Melissa Joyner, Lilie Lin, Lois M Ramondetta, Andrew M Futreal, Kathleen M Schmeler, Geena Mathew, Stephanie Dorta-Estremera, Jianhua Zhang, Xiaogang Wu, Nadim J Ajami, Matthew Wong, Cullen Taniguchi, Joseph F Petrosino, K Jagannadha Sastry, Pablo C Okhuysen, Sara A Martinez, Lin Tan, Iqbal Mahmud, Philip L Lorenzi, Jennifer A Wargo, Ann H Klopp

Faculty, Staff and Student Publications

Tumor microbiota can produce active metabolites that affect cancer and immune cell signaling, metabolism, and proliferation. Here, we explore tumor and gut microbiome features that affect chemoradiation response in patients with cervical cancer using a combined approach of deep microbiome sequencing, targeted bacterial culture, and in vitro assays. We identify that an obligate L-lactate-producing lactic acid bacterium found in tumors, Lactobacillus iners, is associated with decreased survival in patients, induces chemotherapy and radiation resistance in cervical cancer cells, and leads to metabolic rewiring, or alterations in multiple metabolic pathways, in tumors. Genomically similar L-lactate-producing lactic acid bacteria commensal to other …

Usp38 Exacerbates Atrial Inflammation, Fibrosis, And Susceptibility To Atrial Fibrillation After Myocardial Infarction In Mice, Yang Gong, Tingting Yu, Wei Shuai, Tao Chen, Jingjing Zhang, He Huang

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BACKGROUND: Inflammation plays an important role in the pathogenesis of atrial fibrillation (AF) after myocardial infarction (MI). The role of USP38, a member of the ubiquitin-specific protease family, on MI-induced atrial inflammation, fibrosis, and associated AF is unclear.

METHODS: In this study, we surgically constructed a mouse MI model using USP38 cardiac conditional knockout (USP38-CKO) and cardiac-specific overexpression (USP38-TG) mice and applied biochemical, histological, electrophysiological characterization and molecular biology to investigate the effects of USP38 on atrial inflammation, fibrosis, and AF and its mechanisms.

RESULTS: Our results revealed that USP38-CKO attenuates atrial inflammation, thereby ameliorating fibrosis, and abnormal electrophysiologic properties, …

Microplastics In Different Tissues Of A Commonly Consumed Fish, Mohammad Belal Hossain, Farjana Haque Pingki, Md Abdus Samad Azad, As-Ad Ujjaman Nur, Partho Banik, Bilal Ahamad Paray, Takaomi Arai, Jimmy Yu

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Microplastics (MPs) ingestion by fish signifies a worldwide threat to human health but limited research has examined their existence within the consumable portions (muscle) of fish. Thus, this study was undertaken to unveil the prevalence, characterization, and contamination extent of MPs across various body tissues, including the muscle of the king mackerel (S. guttatus) from the lower Meghna estuary in Bangladesh-a pioneering investigation in this region. In our analysis, we identified a total of 487 MPs, with an average abundance of 48.7 ± 20.3 MPs/individual. These MPs were distributed across different tissues, with respective concentrations of 0.84 ± …

Single-Cell Analysis Differentiates The Effects Of P53 Mutation And P53 Loss On Cell Compositions Of Oncogenic Kras-Driven Pancreatic Cancer, Xinlei Sun, Daowei Yang, Yang Chen

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Pancreatic ductal adenocarcinoma (PDAC) is a devastating malignant disease with a dismal prognosis. In the past decades, a plethora of genetically engineered mouse models (GEMMs) with autochthonous pancreatic tumor development have greatly facilitated studies of pancreatic cancer. Commonly used GEMMs of PDAC often harbor the oncogenic KRAS driver mutation (KrasG12D), in combination with either p53 mutation by knock-in strategy (Trp53R172H) or p53 loss by conditional knockout (Trp53cKO) strategy, in pancreatic cell lineages. However, the systematic comparison of the tumor microenvironment between KrasG12D; Trp53R172H (KPmut) mouse models and KrasG12D; Trp53cKO (KPloss) mouse models …

The Importance Of A Healthy Microbiome In Pregnancy And Infancy And Microbiota Treatment To Reverse Dysbiosis For Improved Health, Herbert L Dupont, Madeleine Mary Hines Salge

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BACKGROUND: The microbiome of newborn infants during the first 1000 days, influenced early on by their mothers' microbiome health, mode of delivery and breast feeding, orchestrates the education and programming of the infant's immune system and determines in large part the general health of the infant for years.

METHODS: PubMed was reviewed for maternal infant microbiome health and microbiota therapy in this setting with prebiotics, probiotics, vaginal seeding and fecal microbiota transplantation (FMT).

RESULTS: A healthy nonobese mother, vaginal delivery and strict breast feeding contribute to microbiome health in a newborn and young infant. With reduced microbiome diversity (dysbiosis) during …

An Overview Of The Immune Modulatory Properties Of Long Non-Coding Rnas And Their Potential Use As Therapeutic Targets In Cancer, Moises Martinez-Castillo, Abdelrahman M Elsayed, Gabriel López-Berestein, Paola Amero, Cristian Rodríguez-Aguayo

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Long non-coding RNAs (lncRNAs) play pivotal roles in regulating immune responses, immune cell differentiation, activation, and inflammatory processes. In cancer, they are gaining prominence as potential therapeutic targets due to their ability to regulate immune checkpoint molecules and immune-related factors, suggesting avenues for bolstering anti-tumor immune responses. Here, we explore the mechanistic insights into lncRNA-mediated immune modulation, highlighting their impact on immunity. Additionally, we discuss their potential to enhance cancer immunotherapy, augmenting the effectiveness of immune checkpoint inhibitors and adoptive T cell therapies. LncRNAs as therapeutic targets hold the promise of revolutionizing cancer treatments, inspiring further research in this field …

Endoscopic Ultrasound-Guided Fiducial Placement For Stereotactic Body Radiation Therapy In Patients With Pancreatic Cancer, Irina M Cazacu, Ben S Singh, Rachael M Martin-Paulpeter, Sam Beddar, Stephen Chun, Emma B Holliday, Albert C Koong, Prajnan Das, Eugene J Koay, Cullen Taniguchi, Joseph M Herman, Manoop S Bhutani

Faculty, Staff and Student Publications

Accurate delivery of stereotactic body radiotherapy (SBRT) to pancreatic tumors relies on successful EUS-guided placement of fiducial markers. The aim of this study is to report the technical feasibility and safety of EUS-guided fiducial placement and to evaluate the characteristics and technical benefit of SBRT in a cohort of patients with pancreatic cancer (PC). A retrospective chart review was performed for all (n = 82) PC patients referred for EUS-guided fiducial placement by a single endosonographer at a tertiary cancer center. Data regarding EUS-related technical details, SBRT characteristics, adverse events, and continuous visibility of fiducials were recorded and analyzed. …

Helpful, Unnecessary, Or Harmful: A Systematic Review Of The Effects Of Prescription Drug Monitoring Program Use On Opioid Prescriptions, Nina Z.Y. Smith, J. Douglass Thornton, Susan H. Fenton, Debora Simmons, Tiffany Champagne-Langabeer

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Prescription drug misuse is a global problem, especially in the United States (US). Clinician involvement is necessary in this crisis, and prescription drug monitoring programs (PDMPs) are a recommended tool for the prevention, recognition, and management of prescription opioid misuse. However, because of the plethora of differences between different PDMPs, research on their effects is mixed. Yet, despite varied evidence, policy on PDMP use is trending stricter and more comprehensive. We aimed to identify patterns in the research to inform clinicians and policy. Through a systematic review of four literature databases (CINAHL, Cochrane Database, Embase, and Medline/OVID), we found 56 …

Biom-55. Targeted Gene Expression Profiling Predicts Meningioma Outcomes And Radiotherapy Responses, William Chen, Abrar Choundhury, Narj W. Youngblood, Mei-Yin Polly, Calixto-Hope Lucas, Kanish Mirchia, Sybren Maas, Abigail Suwala, Minhee Won, James Bayley, Akdes Harmanci, Arif Marmanci, Tiemo Kilsch, Minh Nguyen, Harish Vasudevan, Katy Mccortney, Tai-Chung Lam, Jenny Kan-Suen Pu, Lai-Fung Li, Gilberto Ka-Kit Leung, Jason Chan, Haley Perlow, Joshua Palmer, Anna Berghoff, Matthias Preusser, Theodore Nicolaides, Christian Mawrin, Jacob Young, Lauren Boreta, Steve Braunstein, Jessica Schulte, Nicolas Butowski, Sandro Santagatta, Nancy Ann Oberheim Bush, Javier Vallaneuva-Meyer, James P. Chandler, David Solomon, Leland Rogers, Stephanie Pugh, Minesh Mehta, Penny Sneed, Michael Berger, Craig Horbinski, Michael Mcdrmott, Arie Perry, Wenya Linda Bi, Akash Patel, Felix Sahm, Stephen Magill, David Raleigh

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INTRODUCTION

Improvements in meningioma risk stratification are needed and current indications for postoperative radiotherapy are controversial. Here we report multicenter clinical and analytical validation of a gene expression biomarker using clinical and genomic data from 1856 meningiomas from 12 institutions across 3 continents. METHODS

A previously-developed 34-gene expression biomarker was applied to 3 validation cohorts: (1) a multicenter retrospective clinical validation cohort (N = 6 centers, N = 866 meningiomas, median follow-up 5.2 years), (2) a prospective investigator-blinded clinical validation cohort from RTOG 0539 (N = 103 meningiomas, median follow-up 8.4 years), and (3) an analytical validation cohort for test/re-test …

A Longitudinal Study Of Polygenic Score And Cognitive Function Decline Considering Baseline Cognitive Function, Lifestyle Behaviors, And Diabetes Among Middle-Aged And Older Us Adults, Tingting Liu, Changwei Li, Ruiyuan Zhang, Eugenia Flores Millender, Hongyu Miao, Michael Ormsbee, Jinzhen Guo, Adrianna Westbrook, Yang Pan, Jing Wang, Tanika N Kelly

Faculty, Staff and Student Publications

Background: Genomic study of cognition decline while considering baseline cognition and lifestyle behaviors is scarce. We aimed to evaluate the impact of a polygenic score for general cognition on cognition decline rate, while considering baseline cognition and lifestyle behaviors, among the general population and people with diabetes, a patient group commonly affected by cognition impairment.

Methods: We tested associations of the polygenic score for general cognition with annual changing rates of cognition measures in 8 years of follow-up among 12,090 White and 3100 Black participants of the Health and Retirement Study (HRS), a nationally representative sample of adults aged 50 …

Recurrent Somatic Copy Number Alterations And Their Association With Oncogene Expression Levels In High-Grade Ovarian Serous Carcinoma, Hillary P Esplen, Richard K Yang, Awdhesh Kalia, Zhenya Tang, Guilin Tang, L Jeffrey Medeiros, Gokce A Toruner

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Somatic copy number alterations (SCNAs) are frequently observed in high-grade ovarian serous carcinoma (HGOSC). However, their impact on gene expression levels has not been systematically assessed. In this study, we explored the relationship between recurrent SCNA and gene expression using The Cancer Genome Atlas Pan Cancer dataset (OSC, TCGA, PanCancer Atlas) to identify cancer-related genes in HGOSC. We then investigated any association between highly correlated cancer genes and clinicopathological parameters, including age of diagnosis, disease stage, overall survival (OS), and progression-free survival (PFS). A total of 772 genes with recurrent SCNAs were observed. SCNA and mRNA expression levels were highly …

Transforming Ovarian Cancer Care By Targeting Minimal Residual Disease, Amir A Jazaeri, Rachel Grisham, Anne Knisely, Stefani Spranger, Dmitriy Zamarin, R Tyler Hillman, Barrett C Lawson, Kathleen H Burns, Sanghoon Lee, Shannon N Westin, Enrico Moiso, Marc J Williams, Neelkanth M Bardhan, Thomas Pisanic, Ursula Matulonis, Britta Weigelt, Ieming Shih, Panagiotis A Konstantinopoulos, Stephanie Gaillard, Linghua Wang, Carol Aghajanian, Alan D D'Andrea, Paula Hammond, Sohrab Shah, Kai W Wucherpfennig, Karen H Lu

Faculty, Staff and Student Publications

Frontline treatment and resultant cure rates in patients with advanced ovarian cancer have changed little over the past several decades. Here, we outline a multidisciplinary approach aimed at gaining novel therapeutic insights by focusing on the poorly understood minimal residual disease phase of ovarian cancer that leads to eventual incurable recurrences.